tbuckley/cabot-search huggingface dataset:
Impact of metformin on clinical outcomes in advanced hepatocellular carcinoma treated with immune checkpoint inhibitors.
Authors: Lana Khalil, Sandra Kang, Ashley McCook-Veal, Amber Draper, Maria Diab, Walid Labib Shaib, Olatunji B. Alese, Bassel F. El-Rayes, Mehmet Akce
Journal: Journal of Clinical Oncology (2022)

4118 Background: Non-alcoholic steatohepatitis (NASH) is an emerging etiology for hepatocellular carcinoma (HCC) and contributes to the increasing incidence of HCC worldwide. Patients with NASH often have risk factors of metabolic syndrome including hypertension, obesity, and type 2 diabetes (T2DM). NASH induced HCC has been shown to be associated with less response to immune check point inhibitors (ICIs) in HCC. Anti-diabetic agent metformin has been shown to be associated with improved outcomes in patients treated with ICIs in melanoma and non-small cell lung cancer. However, the impact of metformin on the efficacy of ICIs is not well defined in HCC. The main purpose of this study was to examine the effect of metformin on clinical outcomes in patients with advanced HCC treated with ICIs. Methods: We performed a retrospective analysis of patients with advanced HCC treated with ICIs in first and later-line settings between 2015 and 2021. The primary endpoints were overall survival (OS), progression free survival (PFS), and objective response rate (ORR) as assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Patients were stratified based on their usage of metformin. OS and PFS were analyzed using Cox proportional hazard models and Kaplan-Meier analysis with log-rank test. Results: A total of 111 patients met inclusion criteria, 18 patients in the metformin group and 93 patients in the non-metformin group. Most common cause of HCC was viral hepatitis (52%), followed by NASH (29%), alcohol (8%) and other (11%). Baseline characteristics between the two groups were similar except all patients in the metformin group had a diagnosis of T2DM. ORR was 5.6%. (1 partial response) in the metformin group vs 22.6% (5 complete responses, 16 partial responses) in the non-metformin group. Median OS was 45.9 months in the non-metformin group vs 10.8 months in metformin group (HR 1.99, 95% CI 0.95-4.21, p = 0.064). Median PFS of 6.6 months vs 2.5 months (HR 1.75, 95% CI 0.93-3.29, p = 0.077). Moreover, metformin usage was associated with shorter median OS of 10.8 months (HR 1.96, 95% CI 0.75-5.09, p = 0.16) vs 20.9 months among patients with T2DM. OS was significantly worse in patients with poor ECOG performance status 2-3, MELD score 10-23, higher grade tumor histology, AFP &gt; = 400, and use of IO in later lines of therapy. Conclusions: In this retrospective study metformin use was associated with worse clinical outcomes in advanced HCC patients treated with ICIs.
In Black and Latinx patients, as-needed inhaled glucocorticoids reduced asthma exacerbations at 15 mo
Authors: Matthew B. Stanbrook
Journal: Annals of Internal Medicine (2022)

ACP Journal ClubJune 2022In Black and Latinx patients, as-needed inhaled glucocorticoids reduced asthma exacerbations at 15 moMatthew B. Stanbrook, MD, PhDMatthew B. Stanbrook, MD, PhDToronto Western Hospital, University of Toronto, Toronto, Ontario, Canada (M.B.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/J22-0040 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationIsrael E, Cardet JC, Carroll JK, et al. Reliever-triggered inhaled glucocorticoid in Black and Latinx adults with asthma. N Engl J Med. 2022;386:1505-18. https://pubmed.ncbi.nlm.nih.gov/35213105Clinical Impact RatingsGIM/FP/GP: Pulmonology: Reference1. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2021. Accessed at www.ginasthma.org on 5 Apr 2022. Google Scholar Author, Article, and Disclosure InformationAffiliations: Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada (M.B.S.)Disclosures: The commentator has reported no disclosures of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=J22-0040.This article was published at Annals.org on 7 June 2022.ACP Journal Club is editorially independent from Annals of Internal Medicine. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics June 2022Volume 175, Issue 6Page: JC68KeywordsAllergy and immunologyAsthmaDisclosureGlucocorticoid therapyInfectious disease immunologyInhalationIntent to treat analysisLungsNitric oxideResearch funding ePublished: 7 June 2022 Issue Published: June 2022 Copyright & PermissionsCopyright © 2022 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Successful management of Australian patients with extensive skin field cancerization (ESFC) with widefield volumetric arc radiation therapy (VMAT): Report with 12-month follow-up.
Authors: Walter J Curran, Andrew Potter, Christopher Baker, Stephen Shumack, Robert Sinclair, David Christie, Bradley Wong, Peter Foley, Lynda Spelman, Peter O'Brien
Journal: Journal of Clinical Oncology (2022)

9582 Background: Non-melanomatous skin cancer (NMSC) diagnoses are associated with a high risk of developing new skin cancers in adjacent areas. Patients with extensive skin field cancerization (ESFC) have large areas (generally ≥50cm 2 ) of compromised skin characterized by pre-cancerous actinic keratoses often requiring repeated interventions. Lesion-directed therapies have excellent cure rates, but therapies targeting a wider region have limited durability, including topical agents such as 5-flurouracil. The development of volumetric modulated arc radiation therapy (VMAT) to precisely target large, curved skin surfaces has generated interest in its application to ESFC. This is a report on the efficacy, safety, and cosmetic outcomes of VMAT in the management of patients with ESFC at facilities across five Australian states. Methods: Sixty-three ESFC zones on 60 patients were prescribed widefield VMAT and prospectively enrolled in the National (Australian) Dermatology Radiation Oncology Registry (NDROR). Over 80% of patients had received up to 4 prior non-radiotherapy interventions. Fields included lower and upper limb, face, scalp, or trunk regions. Total widefield VMAT RT doses ranged from 45-50 Gy delivered in 25-30 daily fractions across 5-7 weeks. 3-, 6-, and 12-month follow-up assessments rated the percentage of disease clearance, cosmesis using the Lovett’s scale, and toxicity based on CTCAE. Results: At 12-month follow-up, 97% of treated zones had achieved and maintained clinical success, defined as &gt; 90% field clearance. Five percent of patients exhibited recurrence of original disease, whereas 10% of patients developed a new actinic keratosis or NMSC. Cosmesis was rated as excellent or good in 98% of patients. Most patients exhibited grade 1-2 radiation-induced dermatitis during therapy, which resolved by 3-month follow-up. Grade 3 dermatitis at end of treatment was exhibited in 7% of the patients, which also resolved. Eight percent of patients discontinued treatment due to acute toxicities. The most common persistent toxicity at 12-month follow-up was localized grade 1 xerosis (dryness) at 43% and/or alopecia at 33%. Conclusions: Widefield VMAT achieved very promising clinical success in patients with ESFC for whom other therapies had failed. VMAT yielded favorable cosmetic outcomes, and treatment-related toxicity was manageable and transient in most patients. While additional follow up is necessary, these results demonstrate that widefield VMAT may be an excellent option for some patients with increasingly unmanageable presentations of ESFC.
Anlotinib combined with induction chemotherapy followed by chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: A phase II study.
Authors: Feng Jiang, Xiaozhong Chen, Tongxin Liu, WeiFeng Qin, Shuang Huang, Caineng Cao, Ting Jin, Qifeng Jin
Journal: Journal of Clinical Oncology (2022)

e18071 Background: Necrotic lesion is a negative prognostic factor for nasopharyngeal carcinoma (NPC) while there are few treatment options for it. This study investigated the efficacy and safety of anlotinib (a multi-target tyrosine kinase inhibitor) in combination with induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) in treatment of liquefactive necrosis of NPC. Methods: This is an open-label, single-arm, phase II trial (NCT05232552). Patients with histologically confirmed stage T3-4N2/T1-4N3M0 NPC (AJCC 8th) who had measurable lesions per RECISTv1.1 and received no previous treatment for cancer were enrolled. Other inclusion criteria included 18-70 years old and ZPS 0-2. All patients received docetaxel (75 mg/m², iv, d1), cisplatin (75 mg/m², iv, d1) and anlotinib (12mg, oral, qd, d1-14) every 3 weeks for 3 cycles before CCRT. Chemoradiotherapy was 2 cycles of cisplatin (100 mg/m², iv, d1) and anlotinib (12mg, oral, qd, d1-14) every 3 weeks, concurrently with intensity-modulated radiotherapy (GTV &gt; 66Gy). The primary endpoint was progression-free survival rate at 3 years. Here we report the results of a preliminary analysis. Results: Between January 2021 and September 2021, 34 patients (28 males and 6 females) were enrolled, and the median age was 54 years old. At the data cutoff date on January 24, 2022, all patients were eligible for the evaluation of tumor response with primary and lymph node lesions. 79.4% of the patients (27 of 34) had a response each for primary and lymph node lesions after IC, while 70.6% (20 of 34) achieved complete response in lymph node lesions compared with 29.4% (10 of 34) in primary lesions. At 6 weeks after CCRT, 100.0% of the patients (34 of 34) had a response in primary lesions and 97.1% (33 of 34) in lymph node lesions. The incidence of liquefactive necrosis was 58.8% (20 of 34) and there were 51 necrotic lesions in all. Among those necrotic lesions, 56.9% (29 of 51) and 80.4% (41 of 51) had complete response after IC and CCRT. The average area shrinkage of necrotic lesion after IC and CCRT was 84.5%±0.25, 97.7%±0.06, respectively. The most common adverse events of grade 3 was leucopenia (17.6%) and mucositis (17.6%), and there was 1 patient (2.9%) occurred neutropenia of grade 4. Conclusions: This preliminary analysis indicated that anlotinib combined with IC and CCRT had promising efficacy and favorable tolerance as treatment of liquefactive necrosis of locoregionally advanced NPC.
Evaluation of the ability of Idylla EGFR to differentiate result of ARMS EGFR in gray area and identify rare mutation variants.
Authors: Tian Qiu, Fanshuang Zhang, Bo Zheng, Li Junling, Jianming Ying
Journal: Journal of Clinical Oncology (2022)

e15033 Background: Molecular testing involving Epidermal growth factor receptor ( EGFR) mutations is recommended for patients with non-small cell lung cancer (NSCLC), especially with lung adenocarcinoma, and is nowadays an essential element of precision medicine. Although amplification-refractory mutation system (ARMS) is one of the most commonly used methods for EGFR mutation detection, it can only detect variants in known gene loci and give indistinct results in gray area occasionally, which may be caused by the input of poor DNA quality or low-abundance variants. Idylla EGFR assay can detect 51 EGFR mutations directly from formalin-fixed, paraffin-embedded (FFPE) samples within 2.5 hours with &lt; 2 minutes of hands-on time, without manual data analysis need, whose accurate and robust have been proven among Caucasian and Chinese patients. But the assay’s ability to detect EGFR mutation in low abundance which may lead the result of ARMS EGFR in gray area or rare variants has never been evaluated. Methods: FFPE samples were retrospectively collected from 98 lung cancer patients followed by EGFR testing using the Idylla system, which were also previously assessed with ARMS-PCR. Forty-six of them were in gray area by ARMS-PCR of EGFR and need to be retested by ARMS-PCR or validated by the third method. In another 52 cases, no mutations were found by ARMS-PCR of EGFR, but mutations were found by next-generation sequencing (NGS). The ability of Idylla EGFR to detect cases with result in gray area and rare variants were analyzed. Results: In 46 cases with result in gray area by ARMS-PCR of EGFR, after retesting or validation by the third method, 37 of them had the same result with Idylla mutation test, with an overall concordance of 80.4%. Idylla EGFR test missed 8 mutational cases (22/30), identified 1 mutational case in addition (15/16). Except 2 cases with higher CQ value than 29, which means the poor DNA quality or low quantity input, low mutational abundance maybe the main reason for no mutation identified by Idylla EGFR test. In 52 cases with rare EGFR variants, Idylla EGFR test identified 9 mutational cases, while 4/9 mutational variants beyond the scope of Idylla EGFR test, 2 20ins, 1 L858R and 1 19del. Five of the 9 mutational cases, Idylla test detected 5 different 19dels. The variants of all the 52 cases beyond the scope of ARMS-PCR of EGFR, and ARMS-PCR of EGFR didn’t find mutation. Conclusions: The Idylla system provides a rapid and accurate ability to differentiate result of ARMS-PCR of EGFR in gray area and identify more rare mutation variants which may decrease the repeat testing or validation. But the ability of NGS to find more actionable variants is still important.
Risk factors for postoperative infections after urological surgery: Preliminary results from the national and multicenter TOCUS study
Authors: K. Stessy, H. Robin, P. Bigot, M. Baboudjian, M. Françot, S. De Vergie, J. Rigaud, M. Chapuis, L. Brureau, C. Jousseaume, O. Karray, F. Kosseifi, S. Borojeni, E. Lechevallier, S. Bernardeau, F. Bruyère, B. Gondran-Tellier, M. Vallée
Journal: European Urology (2022)
Pharmacogenetics in the Treatment and Supportive Care of Patients With Cancer
Authors: David S. Craig
Journal: Journal of the National Comprehensive Cancer Network (2022)

For patients undergoing treatment for cancer-induced pain, the identification and evaluation of pharmacogenetic variability may improve outcomes. Metabolism of opioids and other analgesic agents is influenced by patient-specific variables and drug–drug interactions, which often pose clinical challenges. Consultation with a clinical pharmacist or pharmacogenetics specialist is recommended to aid in the interpretation and evaluation of pharmacogenetic test results. The current NCCN Guidelines for Adult Cancer Pain provide pharmacogenetic considerations and recommendations for the treatment and supportive care of this population.
A novel patient-derived organoid model for triple-negative breast cancer patients with residual disease after neoadjuvant chemotherapy for screening personalized drugs.
Authors: Feiyang Liu, Dandan Ma, Qingsong Liu, Xiaowei Qi
Journal: Journal of Clinical Oncology (2022)

e12625 Background: Triple-negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy (NAC) have high risk of recurrence. In this study, we developed a novel organoid culture method for growing TNBC patient samples after NAC, with the goal of generating models that more faithfully recapitulates the key features of the primary tumor for screening personalized drugs. Methods: We established organoid lines derived from TNBC patients who had residual tumors after anthracycline and taxane±platinum based NAC as well as normal human mammary tissues. The histopathology signatures of organoid lines were characterized by H&amp;E staining and immunohistochemistry. The genetic and transcriptional features of organoids were analyzed by targeted sequencing and RNA sequencing. A set of clinical drugs were screened for their ability to suppress cancer organoids in vitro and the consistency was also analyzed between clinical response and drug efficacy of organoid models. Results: A total of 10 cancer organoid lines were successfully established, and cultured stably for more than 4 months. For comparison, 2 organoids derived from normal mammary tissues were generated as well. Our success rate for establishing cancer organoids from TNBC patient samples after NAC was 83% (10 out of 12 samples), and for organoids from normal mammary tissues, it was 100% (2 out of 2 samples). These organoid lines closely recapitulated the histopathology, genetic and transcriptional signature, and intratumor heterogeneity of the primary tissues. We found that active PI3K/AKT/mTOR pathways signaling is always required for cancer organoids from TNBC patient samples after NAC, while Wnt pathway activation is dispensable for generation of them in comparison to the organoid cultures from normal breast tissues. More importantly, we found that the anti-Trop-2 antibody-drug conjugate sacituzumab govitecan (IMMU-132) showed higher sensitivity to most cancer organoids from TNBC patient samples after NAC (8 out of 10 samples) with IC 50 ranging from 0.3 nM to 86 nM in contrast to 5-FU (5 out of 10 samples) with IC 50 ranging from 0.9 μM to 10.2 μM in vitro, whose prodrug capetabine is considered as a standard option in the postneoadjuvant setting. These results were also confirmed in patient-derived tumor xenograft models. The consistency of drug efficacy in the established cancer organoids and the patient responses in the clinic reached to 70% (7 out of 10 samples). Conclusions: We established a novel organoid culture system for TNBC patient samples after NAC, which was potentially a useful platform to explore molecular characteristics of TNBC patients after NAC and discover personalized drugs for intensive treatment.
Protocol requirements and logistical intensity of early-phase clinical trials (EP-CTs).
Authors: Sienna Durbin, Debra Lundquist, Megan Healy, Kaitlyn Lynch, Viola Bame, Tristan Martin, Andrew Johnson, Victoria Turbini, Dejan Juric, Rachel Jimenez, Ryan David Nipp
Journal: Journal of Clinical Oncology (2022)

e18609 Background: EP-CTs are increasingly important options for patients with cancer and often involve intensive monitoring. Characterizing the time burden and logistical intensity of EP-CT protocols could help patients and clinicians make informed decisions about trial participation. Methods: We retrospectively reviewed the electronic health records of consecutive patients enrolled in EP-CTs at Massachusetts General Hospital from 2017-2019 to obtain baseline characteristics (demographics and clinical factors), EP-CT investigational agent (immunomodulatory [IM], targeted inhibitor [TI], antibody drug conjugate [ADC]/chemotherapy prodrug), and logistical intensity (visit frequency required per protocol and presence of extended visits). We defined visit frequency as the number of visits required per protocol within the first 28 days on trial. We defined an extended visit as six or more hours required in clinic on at least one day during the first 28 days on study. We evaluated associations among patient characteristics, investigational agents, logistical intensity, and time spent on trial. Results: Among 421 patients (median age = 63.0 years, 56.9% female, 97.6% metastatic disease), 43.2% were enrolled in IM EP-CTs, 43.0% TI, and 13.8% ADC/chemotherapy prodrug investigational agents. Patients enrolled on ADC/prodrug trials had the highest burden of metastatic disease (mean sites: 2.8 [ADC] vs 2.4 [TI] vs 2.3 [IM], p = 0.007) and oldest age (mean years: 64.0 [ADC] vs 61.7 [IM] vs 58.5 [TI], p = 0.003). However, those on ADC trials had the most days spent on trial (mean days: 78.3 [TI] vs 102.2 [IM] vs 131.8 [ADC], p = 0.003). Patients enrolled on TI trials had the highest required visit frequency compared with those enrolled on other trials (mean visits: 5.5 [TI] vs 5.3 [ADC] vs 5.0 [IM], p = 0.027). Additionally, those on TI trials were most likely to have an extended visit (82.3% [TI] vs 58.2% [IM] vs 29.3% [ADC], p &lt; 0.001) and least likely to receive first in human therapy (38.1% [TI] vs 74.1% [ADC] vs 74.2% [IM], p &lt; 0.001). Conclusions: In this cohort of patients participating in EP-CTs, we found that those enrolled on TI trials had the highest per protocol visit frequency and greatest likelihood of required extended visits. Those on ADC trials spent the most days on trial despite having the highest average age and burden of metastatic disease. These data highlight the time burden and logistical intensity of EP-CTs, underscoring certain trials as especially time intensive, which may help inform trial selection and participation.
A comparison among RIRS and miniPERC for renal stones between 1 and 2 cm using fiber dust: A RCT
Authors: L. Berti, M. Maltagliati, U. Besana, C. Buizza, A. Pacchetti, S. Micali, M.C. Sighinolfi, B. Rocco, G. Bozzini
Journal: European Urology (2022)
Low TMB as predictor for additional benefit from neoadjuvant immune checkpoint inhibition in triple-negative breast cancer.
Authors: Thomas Karn, Carsten Denkert, Julia Rey, Karsten Ernst Weber, Uwe Holtrich, Claus Hanusch, Bruno Valentin Sinn, Paul Jank, Jens Bodo Huober, Jens U. Blohmer, Wolfgang D. Schmitt, Marion van Mackelenbergh, Christian Schem, Elmar Stickeler, Christian Jackisch, Michael Untch, Andreas Schneeweiss, Sibylle Loibl
Journal: Journal of Clinical Oncology (2022)

581 Background: It is commonly anticipated that a high tumor mutational burden (TMB) is a predictor of response to immune checkpoint blockade (ICB). We previously showed that triple-negative breast cancer (TNBC) from the GeparNuevo study with high TMB displayed increased response both to neoadjuvant chemo-ICB with durvalumab but also to chemotherapy alone, with no significant interaction with treatment arm (Karn et al. Ann Oncol 2020). In contrast, we also observed that cases with very low TMB more often displayed a pCR after treatment with chemo-ICB than with chemotherapy alone. This may in fact suggest a benefit of ICB to those TNBC with rather low TMB. Methods: We have analyzed the distant disease-free survival (DDFS) of GeparNuevo patients according to TMB and treatment arm (neoadjuvant chemotherapy plus durvalumab or chemotherapy plus placebo). For TMB (mut/Mb) we applied the identical cutoff of the upper tertile as in our previous analysis. Results: The median follow-up of the time-to-event data was 43.7 months. Data of TMB was available in 149 of 174 patients. We found that within the high-TMB tumors (durvalumab: n=27; placebo: n=23), DDFS was similar between both arms of the trial (durvalumab vs. placebo: HR (hazard ratio) 0.95 [95%CI 0.19-4.69], p=0.95). Strikingly however, within the low-TMB group (durvalumab: n=47; placebo: n=52) we observed a significantly better DDFS in the durvalumab-chemotherapy combination arm, in contrast to the arm treated only with chemotherapy (durvalumab vs. placebo: HR 0.23 [95%CI 0.06-0.79], p=0.02; interaction test for TMB and treatment arm p=0.17). The observation was also robust to alternative TMB cutoffs. Similar results were obtained for invasive disease-free survival. Conclusions: Our results show, in contrast to other published data, that patients with early TNBC and low TMB/neoantigen counts may benefit from short-term neoadjuvant durvalumab treatment, while for those with high TMB, durvalumab plus chemotherapy does not improve efficacy over chemotherapy alone.